The present invention is concerned with intermediates and a process useful in the synthesis of sultamicillin and analogs.
Sultamicillin is the USAN (United States Adopted Name) or so-called generic name for 1,1-dioxopenicillanoyloxymethyl 6-(D-alpha-amino-alpha-phenylacetamido)penicillanate (as named by Godtfredsen et al., U.S. Pat. No. 4,342,772) or 6'-(2-amino-2-phenylacetamido)penicillanoyloxymethyl penicillaanate 1,1-dioxide (as named by Bigham, U.S. Pat. No. 4,244,951). These patents disclose various processes for sultamicillin and analogs, all of which involve the hydrogenolysis or hydrolysis (as appropriate) of an alpha-azido or protected amino group (e.g., benzyloxycarbonylamino, triphenylmethylamino, 2-methoxycarbonyl-1-methylvinyl or dimethylaminocarbonyl-1-methylvinylamino). The Godtfredsen et al. analogs include certain 6-betahalo-1,1-dioxopenicillanoyloxymethyl esters as antibacterial agents. Certain of Godtfredsen's generally disclosed alpha-amino protected, 6-beta-halo precursors also have utility in the present novel process for sultamicillin and analogs. However, in contrast to Godtfredsen et al., the halo group is removed as part of the present novel process.
Jasys has earlier disclosed a related process for sultamicillin and analogs. That process involves hydrogenolysis of 6-halo- and 6,6-dihalo-1,1-dioxopenicillanoyloxymethyl esters wherein the alpha-amino precursor group is azido or a benzyloxycarbonylamino group. See, for example, U.K. patent application No. 2,095,250A having priority to U.S. Pat. Ser. No. 246,456, filed Mar. 23, 1981, now abandoned.